We have demonstrated that the 60 kD protein previously characterized on a subset of T lymphocytes and named "T4", is another example of shared components between the brain and immune system. Thus, we have demonstrated that this cell surface molecule can be cross-linked to 125I labeled AIDS virus envelope and immunoprecipitated by the Mab OKT4 in both T cells and brain. Furthermore, we have mapped the brain distribution pattern of the AIDS virus receptor, T4 in monkey, human and rat brain and shown that it is most enriched in areas of the cortex and the hippocampus which subserves cognition and other higher functions. Our work suggest that the neuropsychiatric effects of AIDS may not, as previously thought, be due to inflammatory processes but may be due to a direct neuronal infection of the virus. We have identified, synthesized, and studied an octapeptide "peptide T", which appears to be the critical attachment area of the AIDS viral envelope. Peptide T and several rationally designed peptide analogs appear to bind with high affinity to the AIDS virus receptor, blocking viral infectivity at very low concentrations. We expect that synthetic peptide heteropolymers employing this core pentapeptide attachment sequence will prove valuable as an approach for a vaccine for AIDS. This method and approach appears useful for exploring the presence of other virus receptors in brain. For example, we have already observed that the Epstein-Barr virus which has been known to use the complement receptor on B cells as a receptor entry protein, may actually infect brain via the same receptor molecule which we have recently identified in brain.